Islands of Calleja
Encyclopedia
The islands of Calleja are a group of neural granule cell
s located within the ventral striatum
in the brains of most animals. This region of the brain is part of the limbic system
, where it aids in the reinforcing effects of reward-like activities. Within most species, the islands are specifically located within the olfactory tubercle
; however, in primates, these islands are located within the nucleus accumbens
, the reward center of the brain, since the olfactory tubercle has practically disappeared in the brains of primates. Both of these structures have been implicated in the processing of incentives as well as addictions to drugs. Projections to and from the islands supplement this knowledge with their involvement in the reward pathways for both cocaine and amphetamines.
. The insula magna, or the major island, of these complexes is located in the medial border of the nucleus accumbens. The ventral group of the islands lies along the pial
border of the basal forebrain
, a region of the frontal lobe
that lies adjacent to the temporal lobe. Due to high concentrations of nitric oxide synthase
, an enzyme
that makes nitric oxide
and includes another enzyme known as NADPH-diaphorase
, the islands can be visualized via NADPH-diaphorase staining. Using this method, the islands have been suggested to be a single heterogeneous cell complex. The exact grouping of these structures is unique across species; however, the shaping of the structures is not the same across the hemispheres of the brain.
, one of the three embryonic structures that eventually become specific parts of the brain, the sub-ventricular zone (SVZ) is a group of cells that develop along the surface of the ventricular
layer of the brain, following the creation of the cortical plate in embryos. The cells generated from this region migrate either radially along or tangentially to radial glia
, the cells that help guide neurons to their targeted destination. These progenitors
from the SVZ are best known for their migration down the rostral migratory stream
to differentiate into the different cells of the olfactory bulb
. However, a separate mass of cells, referred to as the "ventral migratory mass," migrates from the SVZ to the basal forebrain, where it develops into the islands of Calleja.
family is a group of genes encoding certain transcription factors that all begin with the same group of nucleotides that attach to a specific promoter on a DNA strand. Most members of the FOX proteins are typically involved in the formation of certain structures of an embryo, where mutations in these genes are evident through the human developmental disorders that result. Of these genes, the FOXP2 variant was the first to be connected to inherited language and speech disorders. Within the islands of Calleja, FOXP2 gene expression has been observed in the developing basal forebrain of monkeys as well as rodents; furthermore, this gene expression has been viewed alongside the expression of two other transcription factors, PBX3
and MEIS2
. Developing neurons that express these genes originate from the subventricular zone; for this reason, the involvement of all three of these genes is thought to be responsible for determining the final destination of the neurons in the islands of Calleja.
, the nucleus accumbens, and the diagonal band
. Some of the islands contain a "core" of neuropil
, or unmyelinated axons and dendrites, filled with a large cell in some cases. Projections to and from the islands connect the structures to the piriform cortex
, which is responsible for processing smell, as well as areas of the basal forebrain, a region responsible for determining an animal's level of wakefulness. The projections with the piriform cortex align with the rest of the olfactory system, the path beginning in the sensory cells of the nose and then proceeding through the olfactory bulb to regions such as the piriform cortex, olfactory tubercle, and amygdala. However, the projections to the basal forebrain structures actually originate from the smaller outer cells of the island clusters as opposed to the large cells within the "core."
The islands of Calleja receive inputs from the back of the amygdala
, which processes emotional memory, as well as the septum, nucleus accumbens, and piriform cortex. The islands also receive information in the form of dopamine
from the substantia nigra
and ventral tegmental area
, located in the midbrain
of the brainstem. Information traveling from these midbrain structures is triggered in response to rewarding activities or feelings. The islands project to the back of the thalamus
, a region with many responsibilities such as sensory information processing, regulation of wakefulness, and relaying information to the cerebral cortex.
and other surrounding areas by adjusting the degree of dilation of the blood vessels that pass through the islands and the ventral pallidum. This vasodilation is adjusted by the action of nitric oxide. Injection of glutamate
into the islands results in decreases in arterial pressure and heart rate, suggesting that the islands are involved to some degree in the regulation of arterial pressure and heart rate. The islands also inhibit the effects of the sympathetic nervous system
on the cardiovascular system by responding to changes in pressure.
and personality changes. Other behavioral and emotional responses occur as well due to serotonin that interacts with the islands.
s and amphetamine
s take advantage of the reward pathways in that they influence greater releases of dopamine and other neurotransmitters that reinforce the feelings associated with the administration and effects of the drugs. The islands of Calleja become more involved with substances administered through the nose, due to the island's involvement in both olfaction and the reward pathways.
s, passing on information between other brain regions along the same pathway as the islands. In rodents, the islands play a role in reproduction due to the neurons' estrogen-binding capacity and the structure's ability to concentrate estradiol
. They also play a role in the reward pathways and processing pheromone inputs from the nose.
Granule cell
In neuroscience, granule cells refer to tiny neurons that are around 10 micrometres in diameter. Granule cells are found within the granular layer of the cerebellum , the dentate gyrus of the...
s located within the ventral striatum
Ventral striatum
The ventral striatum is generally considered that part of the striatum that is connectionally associated with limbic structures, such as the amygdala, hippocampus, midline thalamus, and certain regions of the prefrontal cortex...
in the brains of most animals. This region of the brain is part of the limbic system
Limbic system
The limbic system is a set of brain structures including the hippocampus, amygdala, anterior thalamic nuclei, septum, limbic cortex and fornix, which seemingly support a variety of functions including emotion, behavior, long term memory, and olfaction. The term "limbic" comes from the Latin...
, where it aids in the reinforcing effects of reward-like activities. Within most species, the islands are specifically located within the olfactory tubercle
Olfaction
Olfaction is the sense of smell. This sense is mediated by specialized sensory cells of the nasal cavity of vertebrates, and, by analogy, sensory cells of the antennae of invertebrates...
; however, in primates, these islands are located within the nucleus accumbens
Nucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...
, the reward center of the brain, since the olfactory tubercle has practically disappeared in the brains of primates. Both of these structures have been implicated in the processing of incentives as well as addictions to drugs. Projections to and from the islands supplement this knowledge with their involvement in the reward pathways for both cocaine and amphetamines.
Location
The islands of Calleja are specifically located within the ventral and medial lining of the ventral striatum in the brain, meaning that they lie towards the front and middle of this region within the temporal lobeTemporal lobe
The temporal lobe is a region of the cerebral cortex that is located beneath the Sylvian fissure on both cerebral hemispheres of the mammalian brain....
. The insula magna, or the major island, of these complexes is located in the medial border of the nucleus accumbens. The ventral group of the islands lies along the pial
Pia mater
Pia mater often referred to as simply the pia, is the delicate innermost layer of the meninges, the membranes surrounding the brain and spinal cord. The word finds its roots in Latin, meaning literally "tender mother." The other two meningeal membranes are the dura mater and the arachnoid mater....
border of the basal forebrain
Basal forebrain
The basal forebrain is a collection of structures located ventrally to the striatum. It is considered to be the major cholinergic output of the central nervous system . It includes a group of structures that lie near the bottom of the front of the brain, including the nucleus basalis, diagonal band...
, a region of the frontal lobe
Frontal lobe
The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...
that lies adjacent to the temporal lobe. Due to high concentrations of nitric oxide synthase
Nitric oxide synthase
Nitric oxide synthases are a family of enzymes that catalyze the production of nitric oxide from L-arginine. NO is an important cellular signaling molecule, having a vital role in many biological processes...
, an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that makes nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
and includes another enzyme known as NADPH-diaphorase
NADPH dehydrogenase
In enzymology, a NADPH dehydrogenase is an enzyme that catalyzes the chemical reactionThe 3 substrates of this enzyme are NADPH, H+, and acceptor, whereas its two products are NADP+ and reduced acceptor....
, the islands can be visualized via NADPH-diaphorase staining. Using this method, the islands have been suggested to be a single heterogeneous cell complex. The exact grouping of these structures is unique across species; however, the shaping of the structures is not the same across the hemispheres of the brain.
Etymology
The islands of Calleja are named after Julián Calleja y Sánchez, the Spanish anatomist, who studied the structure prior to publishing a paper in 1893 entitled "La región olfactorie de cerebro" ("The olfactory region of the brain"). Although the structure was named after him, Calleja was not the first to study it. Sigbert Ganser, a German psychiatrist, published a paper in 1882 that discussed the region. Furthermore, the current accepted definition of the islands of Calleja is not the same as the region Calleja himself studied. He was examining the thick portions of the cell layer of the olfactory tubercle rather than the granule cells that bear his name today.Sub-ventricular Zone
Originating from the lateral ganglionic eminenceGanglionic eminence
In neuroanatomy and neuroembryology, a ganglionic eminence is a transitory brain structure present in the embryonic and fetal stages of brain development. The eminences are found in the ventral part of the telencephalon, where they form bulges in the ventricles. These bulges develop into the basal...
, one of the three embryonic structures that eventually become specific parts of the brain, the sub-ventricular zone (SVZ) is a group of cells that develop along the surface of the ventricular
Ventricular system
The ventricular system is a set of structures containing cerebrospinal fluid in the brain. It is continuous with the central canal of the spinal cord.-Components:The system comprises four ventricles:* right and left lateral ventricles* third ventricle...
layer of the brain, following the creation of the cortical plate in embryos. The cells generated from this region migrate either radially along or tangentially to radial glia
Radial glia
Radial glial cells are a pivotal cell type in the developing central nervous system involved in key developmental processes, from patterning and neuronal migration to their recently discovered role as precursors during neurogenesis. They arise early in development from neuroepithelial cells...
, the cells that help guide neurons to their targeted destination. These progenitors
Progenitor cell
A progenitor cell is a biological cell that, like a stem cell, has a tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its "target" cell...
from the SVZ are best known for their migration down the rostral migratory stream
Rostral migratory stream
The rostral migratory stream is a pathway found in the brain of some animals along which neuronal precursors that originated in the subventricular zone of the brain migrate to reach the main olfactory bulb . This pathway has been studied in the rodent, rabbit, and both the squirrel and rheusus...
to differentiate into the different cells of the olfactory bulb
Olfactory bulb
The olfactory bulb is a structure of the vertebrate forebrain involved in olfaction, the perception of odors.-Anatomy:In most vertebrates, the olfactory bulb is the most rostral part of the brain. In humans, however, the olfactory bulb is on the inferior side of the brain...
. However, a separate mass of cells, referred to as the "ventral migratory mass," migrates from the SVZ to the basal forebrain, where it develops into the islands of Calleja.
FOXP2 gene expression
The FoxFOX proteins
FOX proteins are a family of transcription factors that play important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation, and longevity...
family is a group of genes encoding certain transcription factors that all begin with the same group of nucleotides that attach to a specific promoter on a DNA strand. Most members of the FOX proteins are typically involved in the formation of certain structures of an embryo, where mutations in these genes are evident through the human developmental disorders that result. Of these genes, the FOXP2 variant was the first to be connected to inherited language and speech disorders. Within the islands of Calleja, FOXP2 gene expression has been observed in the developing basal forebrain of monkeys as well as rodents; furthermore, this gene expression has been viewed alongside the expression of two other transcription factors, PBX3
PBX3
Pre-B-cell leukemia transcription factor 3 is a protein that in humans is encoded by the PBX3 gene.-Further reading:...
and MEIS2
MEIS2
Homeobox protein Meis2 is a protein that in humans is encoded by the MEIS2 gene....
. Developing neurons that express these genes originate from the subventricular zone; for this reason, the involvement of all three of these genes is thought to be responsible for determining the final destination of the neurons in the islands of Calleja.
Structure and Neuronal Pathways
In rodents, the islands of Calleja are composed of seven distinct clusters within the olfactory tubercle, with the major island creating a border between the septumSeptum pellucidum
The septum pellucidum , and not to be confused with the medial septum, is a thin, triangular, vertical membrane separating the anterior horns of the left and right lateral ventricles of the brain...
, the nucleus accumbens, and the diagonal band
Diagonal band of Broca
The diagonal band of Broca forms the medial margin of the anterior perforated substance.-Contents:It consists of fibers that are said to arise in the parolfactory area, the gyrus subcallosus and the anterior perforated substance, and course backward in the longitudinal striae to the dentate gyrus...
. Some of the islands contain a "core" of neuropil
Neuropil
In neuroanatomy, a neuropil, which is sometimes referred to as a neuropile, is a region between neuronal cell bodies in the gray matter of the brain and blood-brain barrier . It consists of a dense tangle of axon terminals, dendrites and glial cell processes...
, or unmyelinated axons and dendrites, filled with a large cell in some cases. Projections to and from the islands connect the structures to the piriform cortex
Piriform cortex
In anatomy of animals, the piriform cortex, or pyriform cortex is a region in the brain.-Anatomy and function:The piriform cortex is part of the rhinencephalon situated in the telencephalon....
, which is responsible for processing smell, as well as areas of the basal forebrain, a region responsible for determining an animal's level of wakefulness. The projections with the piriform cortex align with the rest of the olfactory system, the path beginning in the sensory cells of the nose and then proceeding through the olfactory bulb to regions such as the piriform cortex, olfactory tubercle, and amygdala. However, the projections to the basal forebrain structures actually originate from the smaller outer cells of the island clusters as opposed to the large cells within the "core."
The islands of Calleja receive inputs from the back of the amygdala
Amygdala
The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...
, which processes emotional memory, as well as the septum, nucleus accumbens, and piriform cortex. The islands also receive information in the form of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
from the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
and ventral tegmental area
Ventral tegmentum
The ventral tegmentum , better known as the ventral tegmental area , is a group of neurons located close to the midline on the floor of the midbrain...
, located in the midbrain
Mesencephalon
The midbrain or mesencephalon is a portion of the central nervous system associated with vision, hearing, motor control, sleep/wake, arousal , and temperature regulation....
of the brainstem. Information traveling from these midbrain structures is triggered in response to rewarding activities or feelings. The islands project to the back of the thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
, a region with many responsibilities such as sensory information processing, regulation of wakefulness, and relaying information to the cerebral cortex.
Receptor proteins
- Bcl-2Bcl-2Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in...
: The cells within the islands of Calleja that contain the Bcl-2 marker exhibit neuronal immaturity. They are numerous in the islands and are thought to aid in developing pathways for specific response. - Cannabinoid receptor CB2: The cannabinoid receptorCannabinoid receptorThe cannabinoid receptors are a class of cell membrane receptors under the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid receptors contain seven transmembrane spanning domains...
s are a class of G protein-coupled receptors that bind either internally or externally produced cannabinoidsCannabinoidsCannabinoids are a class of chemical compounds that include the phytocannabinoids , and chemical compounds that mimic the actions of phytocannabinoids or have a similar structure...
. The CB2 variant was initially believed to be involved only with the cells in the immune system; however, they have been identified in the islands of Calleja and other structures of the limbic system, supporting the idea that this receptor has a neuronal function as well. This function has yet to be determined though. While the CB1 variant of the receptor has a pre-synaptic localization, it is thought that the CB2 receptors may possess a post-synaptic localization. - Dopamine receptor D2Dopamine receptor D2Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity...
: The islands of Calleja are different from other regions in the ventral striatum in that they actually exhibit no expression of this receptor. - Dopamine receptor D3Dopamine receptor D3D dopamine receptor is a protein that in humans is encoded by the DRD3 gene.This gene encodes the D3 subtype of the dopamine receptor. The D3 subtype inhibits adenylyl cyclase through inhibitory G-proteins. This receptor is expressed in phylogenetically older regions of the brain, suggesting that...
: These specific dopamine receptors exhibit different effects on cells depending on their location in the brain. In the islands of Calleja, their presence inversely affects an animal's interest in an unfamiliar area and the animal's tendency to form addictions. These receptors also contribute to the hypothermic response associated with a lowered room temperature in response to the drug EcstasyMethylenedioxymethamphetamineMDMA is an entactogenic drug of the phenethylamine and amphetamine class of drugs. In popular culture, MDMA has become widely known as "ecstasy" , usually referring to its street pill form, although this term may also include the presence of possible adulterants...
. - Muscarinic acetylcholine receptor M4Muscarinic acetylcholine receptor M4The muscarinic acetylcholine receptor M4, also known as the cholinergic receptor, muscarinic 4 , is a protein that, in humans, is encoded by the CHRM4 gene.-Function:...
: The muscarinic acetylcholine receptorMuscarinic acetylcholine receptorMuscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...
s are types of G protein-coupled receptorG protein-coupled receptorG protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
s that regulate the effects of acetylcholineAcetylcholineThe chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
on the nervous system. In rodents, the core of the individual islands of Calleja contains high concentrations of the M4 receptor, whereas the peripheral granule cell clusters have lower concentrations, allowing each island to be easily visualized by staining for this specific receptor. The composition of the M4 receptors in the islands of Calleja in the brains of monkeys is similar to that of rodents; however, many of the islands, besides the major island, do not exhibit a noticeable core structure. - Neurotensin receptorNeurotensin receptorThe neurotensin receptors are transmembrane receptors that bind the neurotransmitter neurotensin. Two of the receptors encoded by the and genes contain seven transmembrane helices and are G protein coupled...
NTS3: NeurotensinNeurotensinNeurotensin is a 13 amino acid neuropeptide that is implicated in the regulation of luteinizing hormone and prolactin release and has significant interaction with the dopaminergic system...
is a neurotransmitter/neuromodulator associated with a number of functions, such as responses to pain, temperature, sleep-wake cycles, and dopamine. NTS3 is identical to the sorting protein sortilinSortilin 1Sortilin is a protein that in humans is encoded by the SORT1 gene. The SORT1 locus shows the strongest association with serum lipoproteins of any genetic locus in the genome. In hepatocytes, sortilin participates in the presecretory degradation of nascent VLDL particles.-Interactions:Sortilin 1 has...
and possesses many other functions outside the central nervous system. NTS3 is expressed in areas that also express the neurotensin receptor NTS1, including the islands of Calleja. - Oxytocin receptorOxytocin receptorThe oxytocin receptor, also known as OXTR, is a protein which functions as receptor for the hormone and neurotransmitter oxytocin. In humans, the oxytocin receptor is encoded by the OXTR gene., which has been localized to human chromosome 3p25....
: OxytocinOxytocinOxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...
is a molecule that induces maternal behaviors in animals. During childbirth, substantial increases in the expression of this receptor occur in the major island of the islands of Calleja. Furthermore, the extent of the increase depends on the mother's previous maternal experience. These changes within the islands of Calleja are connected to the differences in progesteroneProgesteroneProgesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
and estrogenEstrogenEstrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
levels during pregnancy. - PhosphodiesterasePhosphodiesteraseA phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...
7B: Through the degradation of nucleotides, phosphodiesterases (PDE) produce cyclic adenosine monophosphateCyclic adenosine monophosphateCyclic adenosine monophosphate is a second messenger important in many biological processes...
(cAMP), a molecule involved in sensory processing, neural plasticity, learning, and memory. Of the different families of phosphodiesterases, the 7B variant is one that bonds most easily to cAMP. Within the islands of Calleja, PDE7B is involved in the expression of the dopamine receptor D3. It may also be associated with transferring chemical information from the islands to other regions of the brain. - ProkineticinProkineticinProkineticin is a secreted protein that potently contracts gastrointestinal smooth muscle. Recently, Prokineticins have been recognized in humans and other vertebrates. They are thought to be involved in several important physiological processes like neurogenesis, tissue development, angiogenesis,...
: The islands contain the mRNA associated with the PK2 variant of the protein as well as the receptor variant PKR1. This class of proteins and receptors is partially responsible for the neurogenesis of cells in the olfactory bulb and certain reproductive behaviors, such as the hormonal events involved with the reproductive system. - SerotoninSerotoninSerotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
5-HT6 receptor5-HT6 receptorThe 5-HT6 receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gs/Go and mediates excitatory neurotransmission. HTR6 denotes the human gene encoding for the receptor.-Distribution:The 5-HT6 receptor is...
: The serotonin 5-HT6 receptor helps to increase neuronal cAMP production. Within the islands of Calleja and other structures of the striatum, these receptors may play a role in locomotor activity and memory. - SyntrophinSyntrophinThe syntrophins are a family of five 60-kiloDalton proteins that are associated with dystrophin, the protein associated with Duchenne muscular dystrophy and Becker muscular dystrophy. The name comes from the Greek word syntrophos, meaning "companion." The five syntrophins are encoded by separate...
-associated serine/ threonine kinaseSerine/threonine-specific protein kinaseSerine/threonine protein kinases phosphorylate the OH group of serine or threonine .At least 125 of the 500+ human protein kinases are serine/threonine kinases .-Regulation:...
(SAST): Syntrophin is an adaptor proteinAdaptor proteinSignal transducing adaptor proteins are proteins which are accessory to main proteins in a signal transduction pathway. These proteins tend to lack any intrinsic enzymatic activity themselves but instead mediate specific protein–protein interactions that drive the formation of protein complexes...
that connects other signaling proteins to dystrophinDystrophinDystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costamere or the dystrophin-associated protein complex...
, a protein with major associations to muscular dystrophyMuscular dystrophyMuscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...
. The SAST variant SAST124 is found in the islands of Calleja and other regions associated with the islands, such as the sub-ventricular zone and the olfactory bulb.
Function/Suggested Functions
As is the case with many structures of the brain, many of the functions of the islands of Calleja have yet to be confirmed and remain suggestions.Influences on the Cardiovascular System
The islands regulate the amount of blood supplied to the ventral pallidumGlobus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...
and other surrounding areas by adjusting the degree of dilation of the blood vessels that pass through the islands and the ventral pallidum. This vasodilation is adjusted by the action of nitric oxide. Injection of glutamate
Glutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
into the islands results in decreases in arterial pressure and heart rate, suggesting that the islands are involved to some degree in the regulation of arterial pressure and heart rate. The islands also inhibit the effects of the sympathetic nervous system
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
on the cardiovascular system by responding to changes in pressure.
Influences on Neurological Disorders
Changes in behavior due to schizophrenia have been traced back to the high level of D3 dopamine receptors within the islands of Calleja as well as the high concentrations of dopamine passing through them. Damage to the islands due to restricted blood supply has been linked to a condition of amnesiaAmnesia
Amnesia is a condition in which one's memory is lost. The causes of amnesia have traditionally been divided into categories. Memory appears to be stored in several parts of the limbic system of the brain, and any condition that interferes with the function of this system can cause amnesia...
and personality changes. Other behavioral and emotional responses occur as well due to serotonin that interacts with the islands.
Influences on the Reward Pathways
The islands of Calleja are directly connected with some of the major reward centers of the brain. By receiving dopamine inputs from the substantia nigra and the ventral tegmental area, the islands become one of the many regions that process the rewarding feelings associated with this neurotransmitter. The interactions of the islands with the amygdala aid in processing how the body remembers the feelings associated with the release of dopamine. OpioidOpioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
s and amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
s take advantage of the reward pathways in that they influence greater releases of dopamine and other neurotransmitters that reinforce the feelings associated with the administration and effects of the drugs. The islands of Calleja become more involved with substances administered through the nose, due to the island's involvement in both olfaction and the reward pathways.
Other Functions
Some of the neurons within the islands also act as interneuronInterneuron
An interneuron is a multipolar neuron which connects afferent neurons and efferent neurons in neural pathways...
s, passing on information between other brain regions along the same pathway as the islands. In rodents, the islands play a role in reproduction due to the neurons' estrogen-binding capacity and the structure's ability to concentrate estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
. They also play a role in the reward pathways and processing pheromone inputs from the nose.
External links
- Images of Islands of Calleja - brainmaps.org
- Show it! - NeuroNames